Preventive effects of astaxanthin on diethylnitrosamine-induced liver tumorigenesis in C57/BL/KsJ-db/db obese mice.

Aim: Obesity and its related metabolic abnormalities, including oxidative stress and adipokine imbalance, are involved in liver carcinogenesis. The aim of the present study was to examine the effects of astaxanthin, a powerful biological antioxidant, on the development of diethylnitrosamine (DEN)-induced liver tumorigenesis in C57BL/KsJ-db/db (db/db) obese mice.

Methods: Male db/db mice were given a single i.p. injection of DEN (25 mg/kg bodyweight) at 2 weeks of age, and, subsequently, from 4 weeks of age, they were fed a diet containing 200 p.p.m. astaxanthin throughout the experiment.

Results: Twenty weeks of astaxanthin administration significantly inhibited the development of hepatocellular neoplasms (liver cell adenoma and hepatocellular carcinoma) and the hepatic expression of cyclin D1 mRNA compared with the basal diet group in DEN-treated db/db mice. Astaxanthin administration in DEN-treated experimental mice markedly reduced the derivatives of reactive oxygen metabolites/biological antioxidant potential ratio, which is a serum marker of oxidative stress, while increasing the mRNA expression of the antioxidant enzymes superoxide dismutase 2 and glutathione peroxidase 1 in the liver and white adipose tissue. The serum levels of adiponectin increased after astaxanthin administration in these mice.

Conclusion: Dietary astaxanthin prevented the development of liver tumorigenesis in obese mice by improving oxidative stress and ameliorating serum adiponectin level. Therefore, astaxanthin may be useful in the chemoprevention of liver tumorigenesis in obese individuals.